The subjective effects of MDMA and mCPP in moderate MDMA users.

The present study is part of a research program designed to better understand the neurochemical mechanisms underlying the abuse liability of 3,4-methylenedioxymethamphetamine (MDMA) in humans. In these studies, MDMA will be compared to prototypical dopamine (D-amphetamine) and serotonin (meta-chlorophenylpiperazine, mCPP) releasing agents on a variety of measures related to dependence. In order to determine an acceptable dose range (safe but active) of MDMA and mCPP for these studies, moderate MDMA users were administered escalating doses of MDMA (75, 110 and 145 mg/70 kg) and mCPP (17.5, 35 and 52.5 mg/70 kg). Each participant received a single dose under controlled laboratory conditions, i.e. this was a six-group design with a separate group for each dose. There were five participants tested in each group. MDMA increased blood pressure and heart rate whereas mCPP had no effect on these physiological measures. MDMA produced increases in subjective effects indicative of both stimulant (increases in POMS Elation, ARCI Amphetamine, VAS High and Stimulated scale scores) and hallucinogenic effects (increases on five of the six scales of the Hallucinogenic Rating Scale). mCPP produced similar stimulant effects (e.g. increases on POMS Elation, VAS High and Stimulated), as well as hallucinogenic effects (four of the six scales of the Hallucinogenic Rating Scale), which has not been observed in previous studies.

Fingertip reconstruction using two variations of direct-flow homodigital neurovascular island flaps.

The fingertip is an extremely intricate area of digital sensibility that plays an important role in fine perception and hand function. Thus, sensate fingertip reconstruction is essential to the recovery of most hand functions. The authors used two methods of direct-flow homodigital neurovascular island flap coverage to reconstruct distal finger amputations-namely, the triangular-advancement flap technique and the step-advancement flap method. The authors present their experience with these two variations of direct-flow homodigital neurovascular island flaps and their use in reconstructing 18 fingertips and 7 proximal amputation stumps. They did not observe flap failure, and they achieved stable, well-vascularized, appropriate-thickness skin coverage with good sensory properties in all patients. However, they found that the triangular-advancement flap technique was easier to plan and perform than the step-advancement method.

Over-representation of Myers Briggs Type Indicator introversion in social phobia patients.

The purpose of this study is to profile the personalities of patients with social phobia. Sixteen patients with social phobia were compared with a normative population of 55,971, and with 24 hospitalized Major Depressive Disorder inpatients, using the Myers Briggs Type Indicator. The Myers Briggs Type Indicator, a popular personality survey, divides individuals into eight categories: Extroverts versus Introverts, Sensors versus Intuitives, Thinkers versus Feelers, and Judgers versus Perceivers. Social phobia patients were significantly more often Introverts (93.7%) than were subjects in the normative population (46.2%). In addition, using continuous scores, the social phobia patients scored as significantly more introverted than did the patients with Major Depressive Disorder, who also scored as Introverted. Introversion is a major component of social phobia, and this observation may have both etiological and therapeutic significance.

Cognitive impairment and depression predict mortality in medically ill older adults.

BACKGROUND: Depression and cognitive impairment are common in medically ill older adults. Few studies, however, have investigated the roles of both in predicting mortality for medically ill older adults. METHODS: We used a cohort of consecutive patients aged 60 or older admitted to a rehabilitation hospital (N = 667) of whom 455 completed a standardized protocol measuring cognition (Dementia Rating Scale), depression (Geriatric Depression Scale), and disabilities (Functional Independence Measure). Burden of medical illnesses was measured with the Charlson Index. Vital status was assessed one year later. RESULTS: Those subjects who did not complete the screening were more likely to die (24% vs 17%; p = .02) during the one-year follow-up. Of those who completed the screening, male sex (odds ratio [OR] = 1.84), depression (mild OR = 1.64; moderate OR = 2.49), and more severe cognitive impairment (OR = 2.13) predicted mortality independent of age, medical illnesses, or disabilities. No interaction of cognitive impairment and depression was detected. In those subjects cognitively intact, moderate depression (OR = 4.95) and male sex (OR = 3.42) were independent risk factors for dying. In those subjects without depression, male sex (OR = 2.24) and elevated Charlson Index (OR = 1.42) predicted mortality. CONCLUSIONS: Depression and cognitive impairment are independent predictors of one-year mortality in this subgroup of medically ill older adults.

Role of serotonin drugs in the treatment of social phobia.

The use of psychotropic agents (particularly serotonin active drugs) for the treatment of patients suffering from social phobia is reviewed in this report. Several important caveats should be kept in mind when reading this paper. First, the etiology of social phobia is not known; what we currently call social phobia is probably a heterogeneous collection of anxiety syndromes with the common symptomatic theme of interpersonal sensitivity. Second, the mechanism of action of psychotropic medications is not known; drugs which bind at serotonin receptors may, in fact, mediate clinical improvement via an entirely different mechanism. Third, while several agents appear clinically helpful for the treatment of patients suffering from social phobia, there is no drug currently approved by the US Food and Drug Administration for this indication.

Neurobiology of social phobia.

Social phobia is an anxiety disorder that is characterized by excessive fear and/or avoidance of situations in which an individual believes that he or she may be the subject of evaluation or scrutiny while interacting with other people or performing a specific task. This article reviews the available literature on the neurobiology underlying social phobia, including autonomic nervous system effects, neuroimaging findings, pharmacologic challenge studies, and neuroendocrine responsivity and function. Overall, such studies have found few consistently demonstrable differences in neurobiology between patients with social phobia and healthy controls, but further investigations are needed.

A direct-interview family study of generalized social phobia.

OBJECTIVE: The goal of this direct-interview family study was to replicate and extend an earlier finding of a familial liability for social phobia. The authors hypothesized that there would be higher rates of the generalized type of social phobia--but not the nongeneralized (or "discrete") type--among relatives of probands with generalized social phobia. They also hypothesized that rates of avoidant personality disorder, a frequent comorbid condition, would be higher in relatives of probands with generalized social phobia. METHOD: The authors examined rates of three social phobia subtypes defined a priori--discrete, nongeneralized, and generalized--as well as rates of avoidant personality disorder by direct interview of 106 first-degree relatives of 23 patients with generalized social phobia and 74 first-degree relatives of 24 comparison subjects without social phobia. RESULTS: Relative risks for generalized social phobia and avoidant personality disorder were markedly higher (approximately 10-fold) among first-degree relatives of probands with generalized social phobia than among first-degree relatives of comparison probands. In contrast, relative risks for discrete social phobia and nongeneralized social phobia were not significantly different between the two groups of first-degree relatives. CONCLUSIONS: These results confirm earlier findings of a higher rate of social phobia among relatives of probands with generalized social phobia and extend these findings by specifically indicating that it is only the generalized type (and its probable axis II counterpart, avoidant personality disorder) that occurs more often among the families of probands with generalized social phobia. Implications for subsequent genetic studies are discussed.

Short stature, growth hormone deficiency, and social anxiety.

OBJECTIVE: We have reported high rates of social phobia in growth hormone-deficient (GHD) adults who had been treated with growth hormone during childhood. This follow-up study was conducted to determine whether the increased social phobia observed in GHD subjects was secondary to the effects of short stature. METHODS: Twenty-one age- and sex-matched non-GHD short adults were evaluated for social anxiety and compared with the previously studied 21 GHD subjects. RESULTS: Thirty-eight percent (8 of 21) of GHD and 10% (2 of 21) of short subjects met DSM-III-R criteria for social phobia. GHD subjected scored significantly higher than short subjects on the following self-report questionnaires: Fear of Negative Evaluation (p = .03), Fear Questionnaire (p = .01), Social Avoidance and Distress Scale (p = .01), Beck Depression Inventory (p = .007), and the Tridimensional Personality Questionnaire-harm avoidance subscale (p = .0004). CONCLUSIONS: These data suggest that the high prevalence of social phobia in GHD adults is not explained by short stature alone.

Role of serotonin drugs in the treatment of social phobia.

Social phobia is a common anxiety disorder that is underdiagnosed and undertreated. To date, three classes of serotonin drugs have been used to treat patients suffering from social phobia. These include the serotonin selective reuptake inhibitors (SSRIs), the partial 5-HT1A agonist buspirone, and the 5-HT3 antagonist ondansetron. Although none of the serotonin agents have yet been directly compared with the gold standard monoamine oxidase inhibitor phenelzine or the high potency triazolobenzo-diazepines alprazolam or clonazepam, the SSRIs, as a class, appear to be clinically useful agents. Further studies using larger sample sizes and double-blind methodology are needed to clarify the role of serotonin drugs in the treatment of social phobia.

The cutaneous-vulvar clinic revisited: a 5-year experience of the Columbia Presbyterian Medical Center Cutaneous-Vulvar Service.

OBJECTIVE: To review the recent experience of a busy referral cutaneous-vulvar service. STUDY DESIGN: 500 randomly chosen charts from the last 5 years of patients seen at the Columbia Presbyterian Medical Center Cutaneous-Vulvar Service were reviewed. Information was entered into a computer data base and analyzed. RESULTS: The most common presenting condition was vulvar vestibulitis (36.2%), followed by lichen sclerosus (19.2%) and vaginitis/vaginosis (14.8%). Most patients had undergone a variety of therapies prior to referral. Many were treated for moniliasis in the absence of clinical evidence prior to our evaluation. Most patients responded well to appropriate therapy. CONCLUSIONS: A variety of primary care providers see women with cutaneous-vulvar symptomatology. Awareness of prevalent conditions will lead to correct diagnosis and treatment. We emphasize the importance of interdisciplinary consultation in difficult cases.

Clomipramine challenge responses covary with Tridimensional Personality Questionnaire scores in healthy subjects.

Cloninger's Unified Biosocial Theory of Personality postulates a relationship between the relative functional activity of central serotonergic, dopaminergic, and noradrenergic neurotransmitter systems, and the strength of three elemental dimensions of personality. These dimensions are Harm Avoidance, Novelty Seeking, and Reward Dependence, respectively. Accordingly, we predicted that neuroendocrine responses to serotonergic challenge would correlate with Harm Avoidance scores, but not with Novelty Seeking or Reward Dependence scores. We examined the relationship between the prolactin and cortisol responses to a 12.5-mg intravenous clomipramine challenge and these personality dimensions as measured by Cloninger's Tridimensional Personality Questionnaire in 32 healthy subjects. The cortisol response correlated only with Harm Avoidance scores, as predicted; however, prolactin response did not correlate with Harm Avoidance scores. Instead, it demonstrated an inverse relationship with Novelty Seeking scores. There was a positive relationship of baseline prolactin with Harm Avoidance in a post hoc analysis. Cortisol response to serotonergic challenge may be a better indicator for responsivity of serotonergic systems as they relate to the personality dimension of Harm Avoidance than is prolactin. Prolactin responses may be overly affected by dopaminergic influences; however, baseline prolactin may still be a valid indicator of serotonergic tone.

Genital fistulas caused by diverticular disease of the sigmoid colon.

OBJECTIVE: Our purpose was to bring to the attention of gynecologists a subject not mentioned in a single textbook of gynecology, namely, genital fistulas resulting from diverticular disease of the sigmoid colon. STUDY DESIGN: We report our experience with 13 genital fistulas caused by sigmoid diverticulitis. RESULTS: Ten fistulas involved the vagina, one the vagina and bladder, one the tube, and one the uterus. Average age of the patients was 68.6 years (range 54 to 89 years). Presenting symptom in 12 patients was a malodorous vaginal discharge. All with vaginal lesions had previously undergone total hysterectomy. A barium enema failed to demonstrate a fistula in 8 of 11 patients. Colonoscopy failed in 8 of 8 patients. All fistulas were demonstrated by retrograde dye studies. Ten patients operated on were cured. Three patients refused surgery; of these, 1 had intestinal obstruction, 1 may have had spontaneous closure of the fistula, and 1 is being observed. Surgery involved staged procedures in 2 patients, fistulectomy in 4, and bowel resection and anastomosis in 4. CONCLUSIONS: Sigmoidovaginal fistulas are the most prevalent variety of cologenital fistula caused by sigmoid diverticulitis. The diagnosis should be considered in a patient > 50 years old who complains of a foul vaginal discharge and has a history of total hysterectomy. Its presence is best demonstrated by vaginogram. Surgical therapy is advised, the extent of which will rest on the surgeon's judgment of the severity of the inflammatory process found at exploration.

Genital fistulas secondary to diverticular disease of the colon: a review.

Genital fistulas that complicate diverticular disease of the sigmoid colon may no longer be considered esoteric, or even rare phenomena. The vast majority of such lesions present with a foul, often fecal, sometimes purulent and occasionally blood-tinged, vaginal discharge for which patients customarily first seek relief from their gynecologists. Despite this fact, the topic is not mentioned in a single American textbook of gynecology. It is the purpose of this report to review the pertinent literature and to include the authors' experience with 13 additional cases in order to bring this topic to the attention of our gynecologic colleagues.

Links between growth hormone deficiency, adaptation and social phobia.

Children referred for growth hormone (GH) treatment have increased school achievement problems, lack appropriate social skills and show several forms of behavior problems. A multicenter study in the United States has revealed that many GH-impaired children exhibit a cluster of behavioral symptoms involving disorders of mood and attention. Anxiety, depression, somatic complaints and attention deficits have been identified. These symptoms decline in frequency over a period of 3 years, beginning shortly after GH replacement therapy is started. Many of the patients who have received GH and had good growth responses show lower than average quality of life in young adulthood after treatment is completed. GH-deficient adults placed on GH therapy report improvement in psychological well-being and health status, suggesting that GH might have a central neuroendocrine action. Among a group of adults who were GH deficient as children, we find a high incidence of social phobia, a psychiatric disorder linked to GH secretion and usually accompanied by poor life quality. An ongoing study of non-GH-deficient short individuals suggests that short stature is not the cause of this outcome. We conclude that the origins of psychiatric comorbidities, such as social phobia and depression, in GH deficient adults are likely to be neuroendocrine as well as psychosocial.

Evidence for social phobia and other psychiatric disorders in adults who were growth hormone deficient during childhood.

We assessed the psychiatric status of 21 growth hormone deficient (GHD) adults who had been treated with growth hormone (GH) for short stature during childhood. Eight individuals (38%) were found to have undiagnosed social phobia. On a psychometric battery, the scores of GHD subjects with social phobia corresponded closely to those of a matched group of psychiatric patients with social phobia. Because these psychiatric symptoms have deleterious effects on quality of life, social function, and productivity, the physician should be alert to obtain psychiatric assessment of patients with GHD.

The impact of an electroconvulsive therapy consultation service on ECT use at a university teaching hospital.

In order to test the hypothesis that the establishment of a centralized electroconvulsive therapy (ECT) consultation service would affect ECT use at a university teaching hospital, we retrospectively reviewed medical records of patients who received ECT during two 12-month periods preceding and following the institution of a comprehensive ECT consultation service. Data regarding ECT usage, including utilization, types of patients treated, and lengths of stay, were obtained. Patients treated after the institution of a comprehensive ECT consultation service received ECT with less delay, were discharged more quickly after the conclusion of ECT treatment, and had shorter lengths of stay compared with patients who received treatment before the initiation of the service. Following the establishment of the ECT service, the absolute number of patients who received ECT increased, although the rate of ECT use did not change. These findings suggest that the establishment of a comprehensive ECT consultation service may lead to more efficient use of this important treatment in university hospitals and to more cost-effective treatment of some patients with major depression. Additional research is necessary to explore the generalizability of these findings to other treatment settings.

Rearing conditions alter social reactivity and D1 dopamine receptors in high- and low-aggressive mice.

As a result of selective breeding, NC900 mice exhibit isolation-induced attacks in a social interaction test, whereas NC100 mice do not attack but freeze instead. Administration of the D1 receptor agonist dihydrexidine was previously shown to reduce aggression in NC900 mice and nonagonistic approaches in NC100 mice. This resulted from induction of a marked social reactivity in both selected lines. Because isolation rearing also induces social reactivity, the present experiment was designed to test the hypothesis that D1 dopamine receptors mediate isolation-induced social reactivity. Isolation was expected to potentiate the effects of a D1 agonist and to increase D1 dopamine receptor density. Thus, isolated and group-reared mice were administered dihydrexidine, and their social behavior was compared to vehicle-injected controls. Dihydrexidine induced higher levels of reactivity among isolated than among group-reared animals, especially in NC900 mice. In independent experiments, increased densities of D1 dopamine receptors in the striatum of isolated animals were found, with no change in affinity. These studies suggest an important role for the D1 dopamine receptor as a mediator of isolation-induced social reactivity.

Abnormal cervical cytology in adolescents. A 15-year experience.

The onset of sexual activity at a young age (< 17 years) has been identified in several studies as the most important epidemiologic risk factor in the development of cervical intraepithelial neoplasia (CIN). In characterizing the natural history of CIN, investigators have indicated that a percentage of such lesions progress to invasive carcinoma if left untreated. CIN in adolescents was first reported in 1961. The subsequently reported CIN prevalence rates in sexually active, medically indigent teenage populations have increased over time, temporally paralleling increasing early sexual activity among teenagers. In our 15-year experience with abnormal cervical cytology in adolescents, all grades of CIN were observed. Fully 13% of patients had histologically proven CIN 3, a preinvasive lesion. Given reports of an increase in cervical cancer in young women (< 35 years old), the findings of this and similar studies mandate routine cervical cytologic screening in all sexually active teenage girls.

Normal urinary free cortisol and postdexamethasone cortisol in social phobia: comparison to normal volunteers.

In primates, social stress is associated with activation of the hypothalamic-pituitary-adrenal (HPA) axis. Social phobia is a common, often disabling, form of pathological anxiety characterized by marked distress in situations involving possible scrutiny or evaluation. Little is known about HPA function in patients with social phobia. We examined 24-hour excretion of urinary free cortisol (UFC) in 54 patients with social phobia and post-dexamethasone cortisol levels in 64 patients with social phobia and found no evidence of HPA-axis overactivity compared to normal controls, despite pathological levels of anxiety.